Background: Lung cancer is the leading cause of cancer-related death in the male sex worldwide. Non-small cell lung cancer (NSCLC) is the most prevalent type, accounting for 80–85% of cases, and lung adenocarcinoma is the most common and lethal NSCLC subtype, being responsible for ca. 50% of deaths. Despite new therapeutic strategies, lung cancer mortality rates remain high, highlighting the need for the development of new drugs. Objectives: We investigated the pharmacological potential of a series of curcumin-like compounds using two lung adenocarcinoma cell lines as models. Methods and Results: Cell viability assay led to the identification of PQM-214 as the hit compound, and other methodologies were employed to investigate the mechanisms underlying its antitumor potential, including cell cycle analysis, mitotic index determination, assessment of clonogenic capacity, senescence-associated β-galactosidase and annexin V assays, quantitative PCR, and Western blot analyses. The mechanism of action of PQM-214 was investigated in A549 cells, revealing that it effectively inhibits cell proliferation by inducing cell cycle arrest, apoptosis, or senescence. Cell cycle key regulators were significantly modulated by PQM-214, with cyclin E2, MYC, and FOXM1 being downregulated, while senescence markers such as cyclin D1, CDKN1A (p21), IL-8, TIMP1, and TIMP2 were upregulated. Moreover, Western blot results revealed upregulation of cyclin D1 and p21 in PQM-214-treated samples, with a downregulation of cyclin B. Conclusions: PQM-214 seems to act on different molecular targets in lung adenocarcinoma cells, inhibiting cell proliferation and inducing apoptosis. Further studies will be conducted to explore whether PQM-214 can also act as a senolytic agent, which would reinforce its anticancer potential.

A novel hybrid integrating piplartine with a furoxan moiety exhibited a sub-micromolar IC ₅₀ and extraordinary selectivity for PC3 cells, which was associated with its capacity to release NO, generate ROS, induce DNA damage, and trigger apoptosis.

Lung cancer is the leading cause of cancer-related deaths globally, with nonsmall cell lung cancer (NSCLC) being the most prevalent type. Cisplatin and its derivatives are commonly used in classical chemotherapy, but their therapeutic efficacy is limited, and they came with significant side effects. The targeted therapies and immunotherapy have improved survival rates for certain groups of patients. However, overall survival for NSCLC remains very low, which contributes to the high mortality rate. Thus, the search for effective and affordable drugs is ongoing. In this context, ruthenium-based complexes have been extensively studied as promising anticancer agents. In our previous studies, three ruthenium­(II) complexes containing cinnamic acid derivatives with ligands were synthesized and characterized. We demonstrated that the complex [Ru­(trans-4-(trifluoromethyl)­cinnam)­(dppb)­(bipy)]­PF6 effectively inhibited the proliferation of melanoma cells with either an activating N-Ras mutation or a TP53 inactivation mutation. Therefore, in this study, we aimed to evaluate the antitumor potential of complex [Ru­(3,4-cinnam)­(dppb)­(bipy)]­PF6, named CINNAM, against nonsmall cell lung cancer cells A549 (TP53 wild type; K-Ras mutated) and H1299 (TP53 mutated; N-Ras mutated). CINNAM selectively targeted cancer cells over normal cells, with A549 cells showing higher sensitivity to the CINNAM compared to H1299 cells. CINNAM effectively reduced the proliferation of A549 cells by inducing cell cycle arrest at the G0/G1 phase. CINNAM modulated the expression profiles of key cell cycle regulators, CDKN1A, CCND1, and CCNE2. Further, we demonstrated that the cytotoxic activity of CINNAM is linked to its pro-oxidant and pro-apoptotic properties. The interactions of the complex with ct-DNA (calf thymus DNA) were analyzed, and based on the Kb value, the complex present intermediate affinity for DNA. In conclusion, CINNAM exhibits potent antiproliferative and pro-apoptotic effects on NSCLC cells, surpassing those observed with cisplatin.